Phenylepherine, when taken orally by human subjects in adequate dosages (usually in the form of phenylepherine hydrochloride or any other pharmaceutically acceptable salt of phenylepherine), relieves swelling of the mucous membranes of the nose and contiguous respiratory mucosa when this swelling is caused by viral or allergic conditions. It thereby helps restore normal breathing and—by preventing mouth breathing—aids in the restoration of normal ciliary activity in the nasal mucosa which permits draining of retained secretions. However, congestion of the respiratory mucosa is usually accompanied by conditions such as histamine release, excessive coughing, headache, joint pain, and thick tenacious mucus exudates for which antihistamines, pain relieving medication, expectorants, mucus thinning drugs, cough suppressants and other agents are indicated.
However, a single dose of phenylepherine or a pharmaceutically acceptable salt thereof provides a therapeutically effective plasma concentration for 2.5±0.7 hours whereas many agents used in conjunction with phenylepherine provide effective plasma concentrations that differ markedly from this therapeutic profile.
For example, a single dose of an immediate release expectorant such as guaifenesin will usually provide relief for only about one hour, and pain relieving agents and many antihistamines usually provide relief for about 4 to 8 hours per single dose. As a result, there appears to be virtually no benefit in combining phenylepherine with any drug with a noticeably shorter or longer effective period in a single dosage form. Depending on the therapeutic levels attained with the drug used in conjunction with phenylepherine, the phenylepherine will provide the desired therapeutic effect when the other drug has either ceased to be effective, or continues to exert a therapeutic effect which prohibits administration of another dose even though the decongestant effect of phenylepherine has ceased.
It would be desirable if patients suffering from, e.g., respiratory congestion, for which phenylepherine is indicated, would also obtain relief of accompanying symptoms such as excessive coughing, inflammation of the respiratory mucosa and sinus cavities, weeping eyes, bronchitis, rhinitis, rhinorrhea, Eustachian Tube congestion, nausea, headache and joint pain, over a similar time period, by administering a single dose of a dosage form such as, e.g., a tablet, liquid, syrup, suspension, capsule and the like which provides both phenylepherine and one or more other drugs that permits release of the drugs from separate release matrices which are individually formulated for each ingredient's therapeutic profile.
Further, the advent of sustained-release granulation technology has made it possible to achieve and maintain therapeutic levels of a drug at a pre-determined rate, limited only by the normal transit time of orally ingested products through the human alimentary canal. Although this technology has been used to provide sustained-release levels of phenylepherine, the developers of these products have failed to develop a sustained-release or timed-release formulation that provides consistent therapeutic levels of this pharmaceutical agent throughout the dosage periods indicated in the labeling. This failure is evident by the dosages of the products available. These dosages range from 30 to 40 milligrams every 12 hours for an orally ingested sustained-release tablet.
It would be desirable to administer a dosage form, in particular, a sustained-release dosage form, of phenylepherine or a pharmaceutically acceptable salt thereof in better conformity and agreement with the plasma half-life of phenylepherine (2 to 2.5 hours in humans) and the immediate release dosage level of phenylepherine hydrochloride of 10 milligrams every 4 to 6 hours for a daily maximum of 60 mg which is recognized as effective in adults by the United States Food and Drug Administration.